Fehérjék ligandumfelismerésének vizsgálata spektroszkópiai módszerekkel = Investigation of ligand recognition properties of proteins using spectroscopic methods

A pályázati munka során kimutattam két emberi akut-fázis plazmafehérje, az alfa1-savanyú glikoprotein és a szerin proteáz gátló alfa1-antitripszin fehérjeaggregációt gátló, ún. chaperon aktivitását. Bizonyítottam hogy az alfa1-savanyú glikoprotein antiaggregációs funkciója befolyásolható olyan terápiás gyógyszerekkel amelyek a fehérje kötőzsebének nagy affinitású ligandumai. Ezen fehérjék chaperon aktivitásának felismerése új megvilágításba helyezi élettani és kóros folyamatokban játszott szerepüket és felveti annak lehetőségét hogy a lipokalin és szerin proteázgátló fehérjecsaládok további tagjai is rendelkezhetnek ilyen funkcióval. Új kiroptikai spektroszkópiás módszert dolgoztam ki a kismolekula-avidin kötődés kimutatására a 250 nm alatti hullámhossztartományban amellyel avidin ligandumként eddig nem ismert különféle gyógyszer- és természetes vegyület kötődését sikerült kimutatni. Magasabb hullámhossztartományokra kiterjesztett mérések a kismolekula-avidin komplexek részletes jellemzése mellett rámutattak az avidin ligandumkötőhelyén található aromás aminosavoldalláncoknak a kötődésben és ezen keresztül a mért spektrális változásokban (exciton csatolás) betöltött szerepére. A kísérletes adatokat kiegészítő molekulamodellezési eredmények szerint a kötőüreg alján található poláris aminosavakkal létrejövő hidrogénhídkötések meghatározóak a ligandumok stabilizálásában. | In vitro chaperone-like activity of two plasma acute-phase component glycoproteins, the human alfa1-acid glycoprotein (AAG) and the serpin family member alfa1-antitrypsin has been shown for the first time. Both proteins efficiently inhibited heat- and chemical-induced aggregation of various test proteins. The anti-aggregation ability of AAG was abolished/reduced upon drug binding suggesting that protein-protein interactions established between the lipocalin ß-barrel fold of AAG and hydrophobic surfaces of the stressed proteins might be involved in the chaperone-like activity. The results suggest a novel biological function for these proteins and highlight the lipocalin and the serpin superfamily as a possible source of additional intra- and extracellular chaperones. A novel chiroptical spectroscopic approach for detection of promiscuous ligand binding of avidin below 250 nm has been presented. Aromatic residues of the biotin binding pocket render the near-UV circular dichroism spectrum of avidin to be sensitive for ligand binding and are also responsible for induced chiroptical signals via the exciton coupling mechanism. Molecular docking calculations indicated the important role of a polar side-chain cluster at the bottom of the binding cavity in determination of the binding mode of various ligands by formation of hydrogen bondings

Inclusion excluded: Chiroptical sensing of the external surface of sulfated cyclodextrins

It is shown that the heparin antagonist bis-aminoquinoline derivative surfen interacts with sulfated cyclodextrins in a unique fashion. Analysis of the UV spectroscopic data revealed exceptionally strong association (Ka ∼ 107 M-1) of several surfen molecules to the external surface of the cyclodextrin hosts. H-bonded to the sulfate groups in 1:1 stoichiometry, the drug molecules form a chiral layer around the macrocycles. Due to the steric proximity, dipole-dipole coupling occurs between the adjacent aminoquinoline rings that accounts for the large UV hypochromism and the induced exciton couplet in the circular dichroism spectra

Book Review

Elias Aboujaoude and Vladan Starcevic (Eds.) Mental Health in the Digital Age: Grave Dangers, Great Promise, Oxford University Press: New York, NY, 2015, 277 pp. ISBN: 978-0-19-938018-

Book Review

Leonard Reinecke and Mary Beth Oliver (Eds.) The Routledge Handbook of Media Use and Well-Being Routledge, New York, NY, 2017, 465 pp. ISBN: 978-1-138-88658-

The association of celebrity worship with problematic Internet use, maladaptive daydreaming, and desire for fame

Background and aims Celebrity worship, defined as an obsessive fascination with a famous person, has been associated with several mental health problems, such as symptoms of depression and anxiety, dissociation, and body image concerns. The aim of this study was to extend the scope of investigation of previous research on psychological correlates by exploring the association of celebrity worship with compulsive behaviors, such as problematic Internet use, maladaptive daydreaming, desire for fame, and self-efficacy. Methods A voluntary sample of 437 Hungarian adolescents and adults (78.3% male; Mage = 24.7 years, SD = 7.4) completed an online questionnaire focusing on attitudes toward celebrities and other relevant variables. Results As a result of hierarchical regression analyses, high levels of celebrity worship were associated with problematic Internet use, maladaptive daydreaming, and desire for fame. Furthermore, females were at higher risk to become obsessed with celebrities than males. Discussion and conclusion These findings provide with a more comprehensive picture of psychological difficulties associated with celebrity worship and may contribute to a better understanding of this phenomenon

Gender differences in the association between cyberbullying victimization and perpetration: the role of anger rumination and traditional bullying experiences

Studies investigating the similarities and differences in traditional bullying and cyberbullying experiences have demonstrated considerable gender differences concerning its determinants. The aim of the present study was to provide further evidence for the differential role of determinants for males and females by investigating the moderating role of traditional bullying and anger rumination in the relationship of past cyberbullying victimization and recent cyberbullying perpetration in respect to gender. A total of 1500 Hungarian adolescents and adults (57.9% male, Mage = 28.9 years, SD = 8.7) completed an online survey on bullying experiences. Results indicated that males were more likely than females to engage in cyberbullying when they had been previously bullied online. Furthermore, high anger rumination elevated the risk of perpetration among male cyberbullying victims, while repeated victimization in traditional bullying increased the risk of cyberbullying perpetration among females. These results underline the importance of considering gender differences in intervention efforts against bullying

Apparent circular dichroism signature of stirring-oriented DNA and drug–DNA complexes

It is shown that in water with no added salts calf-thymus DNA and its drug-loaded forms exhibit peculiar, completely reversible circular dichroism (CD) spectroscopic changes upon mechanical rotatory stirring. Due to the stirring-induced spatial alignment of the helices, the CD spectra are overwhelmed by the much more intense linear dichroism contribution. This apparent chiroptical response can be generated and detected by an ordinary CD spectropolarimeter without using any sophisticated attachment. It is a technically simple complement to existing methods suitable to obtain additional structural information which can not be derived from isotropic spectra. Drug–DNA interactions generating no or very weak CD spectroscopic changes under isotropic conditions become easily detectable upon stirring the sample solution. Stirring-induced changes of the CD profile also enable to clarify the DNA binding mode of various compounds (e.g., imatinib, thioflavin T) which would remain ambiguous considering isotropic spectral data only

A problémás videojáték-használat újabb elméleti és gyakorlati megközelítései

Napjainkban a videojátékokkal való időtöltés az egyik legnépszerűbb szabadidős tevékenység a fiatalok körében. Ennek elterjedésével párhuzamosan nőtt a tudományos érdeklődés a játékok káros hatásai, illetve azok problémás használata iránt, mely jelenség a köznyelvben csak “játékfüggőségként” ismert. A kutatások rámutattak arra, hogy a játékosok kis része jelentős pszichológiai ártalmaktól szenved számos életterületen (például családi, társas, munkahelyi/tanulmányi). Tanulmányunk célja áttekintést nyújtani a problémás játékhasználat újabb elméleti megközelítéseiről, diagnosztikai kritériumairól és méréséről. A definíciót és a kritériumokat övező tudományos viták mellett bemutatjuk a kezelési eljárásokat és programokat, valamint felvázoljuk a jövőbeli kutatási irányzatok lehetőségeit is.&#x0D; &#x0D; ---&#x0D; &#x0D; Problematic video gaming: Novel approaches in theory and practice&#x0D; &#x0D; These days spending time playing video games is one of the most popular leisure-time activities among young people. With the growth of interest in video games research has begun to focus on the negative effects of usage in addition to problematic use, which is commonly known as "game addiction". Research has pointed out that a small number of gamers suffer from severe functional and psychological harm in several aspects of their lives (for instance, family, social, work/study). The aim of our study is to provide an overview of the novel theoretical approaches, diagnostic criteria and assessment of problematic gaming. Besides describing the scientific debates concerning the definition and criteria, we present the treatment methods and programs, and draw a picture of the possibilities for future directions in research.&#x0D; &#x0D; Keywords: problematic gaming, gaming disorder, addiction, Internet Gaming Disorder (IGD), interactive media</jats:p

Glycosaminoglycans are potential pharmacological targets for classic DNA minor groove binder drugs berenil and pentamidine

It is shown that the antiprotozoal drugs berenil and pentamidine, conventional minor groove binders of DNA, form non-covalent complexes with polyanionic glycosaminoglycans. Induced circular dichroism (CD) spectra as well as UV hypochromism confirmed drug binding to the asymmetric template of heparin and chondroitin 6-sulfate. The biphasic nature of the CD signals refers to intermolecular chiral exciton coupling between the dicationic guest molecules forming a right- or a left-handed helical array along the GAG chains. Quantitative evaluation of the spectroscopic data measured in pH 7.0 buffer solution (80 mM NaCl) indicated a higher (Ka ∼ 106 M-1 for berenil) and a lower (Ka ∼ 105 M-1 for pentamidine) affinity heparin binding of these agents, similar to that reported for DNA. Drug-chondroitin sulfate complexes (Ka ∼ 104-105 M-1) could be detected only at low ionic strength. These results imply that besides nucleic acids, GAGs may be another pharmacological targets for diarylamidine drugs